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In order to design a thermoelectric cooler system with a precise numerical prediction on its working effectiveness, based on forced fluid mechanics theory, heat transfer theory and thermoelectric cooling theory, the paper proposed an optimized design of thermoelectric cooler system with the application of forced air cooling. Combining with the physical model of heat transfer and analysis of the air flow pattern in channel of the whole system, it can predict airflow rate of the cooling channel, heat transfer coefficient and heat transfer efficiency of the cooling metal fin and the specific cooling effectiveness. With this method, it can achieve optimized selection for system components and enhance the efficiency of system. A specific system design example provided in the paper verifies the whole theory in this paper and it basically satisfies the requirement of the thermoelectric cooler system.